New and potent drugs are urgently needed to inhibit uncontrolled growth, invasion and metastasis. The majority of available treatments or therapeutics are limited towards inhibition of the growth of the tumour. Microtubule inhibitors block the mitotic spindle and function of the cytoplasmic microtubule complex and therefore form an interesting alternative for drug development for treating cancer, since they inhibit proliferation, invasion and metastasis. Two examples of such drugs that have been used with success are paclitaxel (Taxol®) and docetaxel (Taxotere®), which have been used to treat roughly one million of patients in the 10 years since they were first approved as anti-cancer drugs. Paclitaxel, docetaxel and vinca alkaloids like vinblastine are compounds interacting with the mitotic spindle by binding to β-tubulin. They are used as therapeutics in standard chemotherapy regimens and in combination with new drugs like the HER2 targeting antibody trastuzumab. But toxicity, drug resistance, and complex galenic formulations are restricting their clinical use in cancer therapy. Further drawbacks of e.g. paclitaxel are its low solubility in water (needs to be dissolved in Cremophor EL (polyoxyethylated castor oil) which causes hypersensitivity reactions), high hydrophobicity, adhesion to plastic tubing inner surfaces complicating administration, creating therapy resistance, etc. . . .
Thus, new tubulin targeting antimitotic agents with better tolerability and efficacy against (late-stage resistant) tumors are urgently needed. The present invention provides solutions to the above-identified problems by designing peloruside-derivatives as new therapeutic agents.